Phytochemical compounds of Morus alba as anti-aging agent towards in silico binding to matrix metalloproteinase proteins

Original Research

Abstract

Skin aging is a natural phenomenon which is related to progressive loss of skin structural integrity and physiological function and affects aesthetics which has been of highly interest. Inhibition of matrix metalloproteinases (MMPs) such as MMP-1, MMP-3, MMP-9 is one of the potential approaches for anti-aging treatment as these targets are involved in molecular pathology to skin aging process from sunlight. The aim of the study was to investigate the binding affinity of 9 phytochemical compounds extracted from Morus alba Moraceae into the MMP enzymes leading to potential anti-aging activity by using in silico approaches including molecular docking and molecular dynamics simulations. All the compounds showed binding abilities into the targets. In particular, mulberrofuran H obtained the best docking results on the three MMPs. Molecular dynamics simulations of the complex of  mulberrofuran H and MMP-9 showed that this complex was stable. Combination of molecular docking and molecular dynamics simulations results, there was an important hydrophobic interaction between mulberrofuran H and His401 at the active site of the MMP-9, which determined the MMP-9 inhibitory potential of mulberrofuran H. The ligand mulberrofuran H was also stabilized into the MMP-9 protein by hydrogen bonds with Pro421 with the high occupancy of 77.67%. These results demonstrated the good binding of mulberrofuran H on the protein MMP-9 which highlighted its anti-aging potency.

Graphical abstract

Virtual Screening, Oriented-synthesis and Evaluation of Lipase Inhibitory Activity of Benzyl Amino Chalcone Derivatives

Original Research

Abstract

Nowadays, obesity has been becoming one of the most popular problems to the global health. Molecular design with the aid of computing method is an efficient and cost-saving solution in the initial research of new potential drugs for the treatment of obesity. This study focused on benzyl amino chalcone derivatives as they have a benzyl group that can mimic the hydrophobic effect of the long chain carbon of Orlistat, a drug used to treat obesity. Initially, 102 molecular structures were prepared and docked into the protein by using AutoDock Vina version 1.5.6. Fourteen structures having good docking scores were selected to synthesize using a Claisen-Schmidt reaction. Afterward, these synthesized chalcones were tested biological activity against pancreatic lipase by spectrophotometric determination at a wavelength of 405 nm, using p-nitro phenyl palmitate as the substrate. The co-crystallized ligand of pancreatic lipase enzyme was redocked into the enzyme and the RMSD was 1.4976 Å which showed the ligand and the protein preparation could regenerate the practical experiment. As the docking results, the binding affinities of top ten compounds varied from -8.6 and -10.2 kcal/mol. Biological testing resulted in 4 derivatives with IC50 >120 µM, 8 derivatives with 60 µM < IC50 < 120 µM and 2 derivatives with IC50 < 60 µM. In addition, the docking results also confirmed the key role of amino acid Ser152 in interacting with the ligands. The benzyl amino chalcone derivatives are required for further investigation to become a lead compound for anti-obesity drug discovery.

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